CXCL12 stim 
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  • ||||||||||  Distinct mechanism of CXCR7 activation in EGFR-mutated NSCLC by chemokines (Section 54) -  Mar 5, 2024 - Abstract #AACR2024AACR_8966;    
    Altogether, our data reveal an SMC chemokine-dependent pathway linking immunological infiltration and sympathetic innervation as a rheostat for BAT maintenance and thermogenesis. Abstract is embargoed at this time.
  • ||||||||||  Journal:  The development of potent, competitive CXCR4 antagonists for the prevention of cancer metastasis. (Pubmed Central) -  Dec 4, 2023   
    Furthermore, IS4 and IS4-FAM inhibited both CXCL12-stimulated cancer cell migration and Ca release in both adherent and suspension cell lines with similar or improved potency as compared to two literature CXCR4 antagonists. Our results highlight the potential of IS4 and IS4-FAM as research tools and as potent CXCR4 antagonists for the prevention of metastasis.
  • ||||||||||  Journal:  Molecular characterization of the CXCR4 (Pubmed Central) -  Nov 24, 2023   
    This study identified a nanobody-drug-conjugate targeting CXCR4 as a putative therapeutic option for GCT, i.e. seminoma and yolk-sac tumors. Furthermore, this study shed light on the functional role of the CXCR4
  • ||||||||||  M7583 / EMD Serono, Telios Pharma
    Evaluation of TL-895, A Novel Bruton (X1) -  Sep 30, 2023 - Abstract #DGHO2023DGHO_658;    
    P1b/2, P2
    TL-895 potently inhibited BTK signaling to reduce cell adhesion and SDF1?-mediated chemotaxis in JAK2 VF cells. These data suggest that TL-895 could inhibit the interactions of JAK2 VF myeloblasts with their microenvironment and may improve patient outcomes in MF, a hypothesis that is currently being evaluated in the clinic (NCT04655118, NCT05280509, NCT04640532).
  • ||||||||||  Journal:  The N-terminus of CXCR4 splice variants determines expression and functional properties. (Pubmed Central) -  May 8, 2023   
    Functional analyses revealed that CXCR4 variants may also affect each other or interact during CXCL12-stimulated cellular responses. Altogether, our results suggest that CXCR4 variants may have distinct functional roles that warrant additional investigation and could contribute to future development of novel drug interventions.
  • ||||||||||  The Tetraspanin CD53 Promotes CXCR4 Signaling to Facilitate B Cell Migration (ENMCC - Hall D) -  Nov 4, 2022 - Abstract #ASH2022ASH_5525;    
    Together, these data support a model whereby CD53 interacts with CXCR4 to promote signaling in B cells. Both normal and malignant B cells rely on CXCL12/CXCR4 signaling for proper trafficking and function, and thus CD53 may represent a novel target for the inhibition of malignant B cells.
  • ||||||||||  burixafor (GPC-100) / GPCR Therap
    GPC-100 Is a Novel CXCR4 Inhibitor That Leads to Improved in Vitro Potency and In Vivo Efficacy in Stem Cell Mobilization When Combined with a Beta-Blocker (ENMCC - Hall D) -  Nov 4, 2022 - Abstract #ASH2022ASH_2823;    
    Previous studies indicate that stress hormones like epinephrine and norepinephrine exert stimulatory effects on cancer progression by modulating tumorigenesis, proliferation, and metastasis via B2AR signaling...Propranolol improved mobilization induced by a single administration of both GPC-100 and AMD3100...Additionally, combination treatment with G-CSF, GPC-100 and Pro may prove to be best-in-class mobilization therapy for ASCT in MM patients, especially those that fail to mobilize with standard of care. As a result, we will initiate a 2 arm, Phase 2 clinical trial evaluating both GPC-100 + Pro, and the triple combination of G-CSF + GPC-100 + Pro in Q4 of 2022.
  • ||||||||||  MK-2206 / Merck (MSD), Aliqopa (copanlisib) / Bayer
    Elongation of Long-Chain Fatty Acids Is Crucial for Hematopoietic Stem Cell Engraftment and Leukemia Propagation (ENMCC - 293-294) -  Nov 4, 2022 - Abstract #ASH2022ASH_1715;    
    By contrast, AKT inhibitor, MK2206, did not alter WT or Elo6KO MA9 cell migration...In summary, this study demonstrates novel and unexpected outcomes in normal HSCs and AML driver-transformed cells following lipid changes induced by Elovl6 deficiency. Altering lipid diversity could be a potential strategy to treat AML.
  • ||||||||||  Journal:  Computational Modeling Implicates Protein Scaffolding in p38 Regulation of Akt. (Pubmed Central) -  Oct 25, 2022   
    However, scaffolding inhibition can potentiate future kinase activity by redistribution of pathway components, potentially amplifying oncogenic signaling. These studies reveal how computational modeling can decipher mechanisms of cross-talk between the p38 and Akt signaling pathways and point to scaffold proteins as central regulators of signaling dynamics and amplitude.
  • ||||||||||  Journal, IO biomarker:  The Emerging Role of MTHFD Family Genes in Regulating the Tumor Immunity of Oral Squamous Cell Carcinoma. (Pubmed Central) -  Jun 14, 2022   
    Moreover, MTHFD family genes were significantly correlated with several immune inhibitory genes such as CD274 and CTLA4 and several immune-stimulatory genes such as CXCL12, CXCR4, and TMIGD2. Given the expression pattern, prognostic value, biological functions, and involvement in tumor immunity, MTHFD family genes could serve as potential therapeutic biomarkers in targeting tumor immunity in oral cancer.
  • ||||||||||  mavorixafor (X4P-001) / X4 Pharma
    CRISPR/CAS9-BASED MODEL OF HETEROZYGOUS CXCR4 WT/R334X MUTATION TO STUDY CELLULAR PHENOTYPES IN WHIM SYNDROME () -  May 13, 2022 - Abstract #EHA2022EHA_2589;    
    Mavorixafor, a CXCR4 antagonist currently in clinical trials for the treatment of patients with WHIM syndrome, was active in an unbiased manner on a spectrum of CXCR4-related functions (ligand binding inhibition, calcium mobilization, ERK activation and chemotaxis) with comparable biological activity and potency in cells expressing the WT and R334X CXCR4 receptor...This observation is consistent with the dominant inheritance pattern of WHIM syndrome. The present study brings several novel insights in CXCR4 WHIM biology and enriches the toolbox of models available for studying WHIM syndrome.
  • ||||||||||  Journal:  CXCL12 promotes CCR7 ligand-mediated breast cancer cell invasion and migration toward lymphatic vessels. (Pubmed Central) -  Apr 12, 2022   
    In the three-dimensional tumor invasion model with lymph networks, CXCL12 stimulation facilitates breast cancer cell migration to CCL21-reconstituted lymphatic networks. These results indicate that CXCL12/CXCR4 signaling promotes breast cancer cell migration and invasion toward CCR7 ligand-expressing intra-tumoral lymphatic vessels and supports CCR7 signaling associated with lymph node metastasis.
  • ||||||||||  progesterone / Generic mfg.
    Journal:  CXCL12 May Drive Inflammatory Potential in the Ovine Corpus Luteum During Implantation. (Pubmed Central) -  Mar 12, 2022   
    We report concurrent increases in CXCL12, CXCR4, and select inflammatory mediators in ovine CL as early pregnancy progresses. We propose CXCL12 stimulates production of select cytokines, rather than P4 in the CL to assist in CL establishment and survival.
  • ||||||||||  Modified tetraazamacrocycles as improved CXCR4 antagonists (In-Person Room (Virtual Room)) -  Jan 28, 2022 - Abstract #ACSSp2022ACS_Sp_1262;    
    The bis-linked complexes are highly efficient antagonists, while single-macrocycle analogues are much less effective. Our objectives were to synthesize analogues of our most effective bis-tetraazamacrocycle metal complexes and to characterize their chemical and physical properties in preparation for determining their antagonism of CXCR4.
  • ||||||||||  5-fluorouracil / Generic mfg.
    Journal:  Pro-pigmentary action of 5-fluorouracil through the stimulated secretion of CXCL12 by dermal fibroblasts. (Pubmed Central) -  Dec 15, 2021   
    While showing prenatal ethanol exposure to have a sexually dimorphic, stimulatory effect on CXCL12 and CXCR4 in LH similar to CCL2 and its receptor, these results reveal their distinct relationship to the peptide neurons, with the former closely related to Hcrt/OX and the latter to MCH, and they link ethanol's actions in LH to a stimulatory effect on neuroprogenitor cells in the NEP. 5-FU possesses a pro-pigmentary activity through activation of the CXCL12/CXCR4 axis to drive the chemotactic migration of melanocytes.
  • ||||||||||  Mozobil (plerixafor) / Sanofi
    Journal:  The CXCL12/CXCR7 signalling axis promotes proliferation and metastasis in cervical cancer. (Pubmed Central) -  Nov 21, 2021   
    CXCR7 silencing or CCX733 treatment rather than CXCR4 silencing or AMD3100 treatment suppressed the proliferation, migration and invasion of cervical cancer cells stimulated by CXCL12...These data support the finding that the downregulation of CXCR7 suppresses the proliferation and metastasis of cervical cancer cells. Inhibition of CXCR7 may be a potential targeted therapy for cervical cancer.
  • ||||||||||  Journal:  CXCL12-stimulated lymphocytes produce secondary stimulants that affect the surrounding cell chemotaxis. (Pubmed Central) -  Sep 18, 2021   
    In contrast, the conditioned medium from CXCL12-stimulated cells suppressed CCR7 ligand-dependent directionality and the cell migration speed of CXCR4-deficient cells. These results suggest that paracrine factors from CXCL12-stimulated cells navigate surrounding cells to CXCL12 by controlling the responsiveness to CCR7 ligand chemokines and CXCL12.
  • ||||||||||  Preclinical, Journal:  Modulatory effect of chemokines on porcine endometrial stromal and endothelial cells. (Pubmed Central) -  Jul 28, 2021   
    The number of capillary-like structures was significantly reduced after CXCL8, CXCL10, and CXCL12 stimulation. In conclusion, among all examined chemokines, CCL2 is thought to act as the modulator of stromal cell functions, whereas CCL4 and CCL8 are suggested to be potent factors directly stimulating blood vessel creation.
  • ||||||||||  Journal:  miR-126-3p is essential for CXCL12-induced angiogenesis. (Pubmed Central) -  Jun 13, 2021   
    Finally, we observed that SPRED-1 (one of miR-126-3p targets) was inhibited after CXCL12 treatment in HUVEC leading to improvement of CXCL12 pro-angiogenic potential in vitro. Our results proved for the first time: 1-the role of CXCL12 in modulation of miR-126 expression; 2-the involvement of miR-126 in CXCL12 pro-angiogenic effects; 3-the involvement of SPRED-1 in angiogenesis induced by miR-126/CXCL12 axis.